Langerhans cells (LC) are bone marrow-derived, immunocompetent cells which comprise 2-6% of the human epidermal cell population. Although these cells have been implicated as playing a major role in contact dermatitis, probably by acting as antigen presenting cells, their exact function(s), in particular their secretory products, is not understood. Moreover, although their numbers are altered in a variety of skin diseases, e.g. lichen planus, mycosis fungoides, AIDS, their role (if any) in these disorders is totally obscure. The experiments proposed in this grant have two major goals: 1) to define the products produced and secreted by LC in short term cultures and to determine which substances influence this production. In particular, supernatants from LC cultures will be assayed for prostaglandin E2, interleukin-1, interleukin-2, tumor necrosis factor and enkephalin; 2) the cells will be assayed for the presence of mRNAs for interleukin-1 and tumor necrosis factor; 3) to establish long term cultures of "pure" LC. These cells will be used to determine whether human LC indeed are antigen presenting cells (e.g. in contact dermatitis). Furthermore, if, as our preliminary results indicate, LC do not express Birbeck granules, experiments will be performed to detect and characterize a possible keratinocyte-generated factor which induces these granules.